Phenotypic and genotypic overlap between mosaic NF2 and schwannomatosis in patients with multiple non-intradermal schwannomas

Human Genetics
Hildegard Kehrer-SawatzkiVictor-Felix Mautner

Abstract

Schwannomatosis and neurofibromatosis type 2 (NF2) are both characterized by the development of multiple schwannomas but represent different genetic entities. Whereas NF2 is caused by mutations of the NF2 gene, schwannomatosis is associated with germline mutations of SMARCB1 or LZTR1. Here, we studied 15 sporadic patients with multiple non-intradermal schwannomas, but lacking vestibular schwannomas and ophthalmological abnormalities, who fulfilled the clinical diagnostic criteria for schwannomatosis. None of them harboured germline NF2 or SMARCB1 mutations as determined by the analysis of blood samples but seven had germline LZTR1 variants predicted to be pathogenic. At least two independent schwannomas from each patient were subjected to NF2 mutation testing. In five of the 15 patients, identical somatic NF2 mutations were identified (33%). If only those patients without germline LZTR1 variants are considered (n = 8), three of them (37.5%) had mosaic NF2 as concluded from identical NF2 mutations identified in independent schwannomas from the same patient. These findings imply that a sizeable proportion of patients who fulfil the diagnostic criteria for schwannomatosis, are actually examples of mosaic NF2. Hence, the molecular ...Continue Reading

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Mar 26, 2019·American Journal of Medical Genetics. Part a·Rosalie E FernerLarry S Sherman
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Jul 18, 2021·Human Mutation·Cristina Perez-BecerrilMiriam J Smith

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Methods Mentioned

BETA
PCR
Exome Sequencing
deamination

Software Mentioned

Human Splicing Finder ( HSF
MutationTaster2
gnomAD
PolyPhen
SIFT

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